Proposed is the synthesis of the first anthracycline analogs that have alterations in the carbon skeleton of the tetracyclic aglycone. Specifically, these alterations will be at the quinone nucleus, a critical site of action for both antitumor and cardiotoxic effects of the anthracyclines. Isosteric structures will be derived by substituting N-oxide and S-oxide bonds for the quinone carbonyls. Evaluation of the proposed isosteres should give information about the nature and origin of antitumor and cardiotixic effects, leading to the possible separation of these effects and greatly improved new anticancer drugs in this series. Proposed targets will be obtained by total synthesis, not by modification of the nature anthracyclines. To facilitate this, design of targets will be based on recent data about structure-activity relationships, which show permissible simplifications in structure. Evaluations will be done both in vitro and in vivo for antitumor properties and related effects.